NCT03177798: MitoCKD

Mitochondria and Chronic Kidney Disease

Completed Phase 2 Results posted Last updated 29 October 2019

What this trial tests

Phase 2 trial testing Icatibant in Hemodialysis-Induced Symptom in 11 participants. Completed in 31 December 2018.

Timeline

1 August 2017

Primary endpoint
30 June 2018

31 December 2018

Quick facts

Lead sponsor	Vanderbilt University Medical Center
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	crossover
Masking	quadruple
Primary purpose	prevention
Enrollment	11
Start date	1 August 2017
Primary completion	30 June 2018
Estimated completion	31 December 2018
Sites	1 location across United States

Drugs / interventions tested

• Icatibant (ICATIBANT) — full drug profile →
• Placebo

Conditions studied

• Hemodialysis-Induced Symptom — all drugs for Hemodialysis-Induced Symptom →
• Mitochondrial Diseases — all drugs for Mitochondrial Diseases →

Sponsor

Vanderbilt University Medical Center

Who can join

Adults 18 to 78, any sex, with Hemodialysis-Induced Symptom or Mitochondrial Diseases. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Phosphocreatine (PCR) Recovery Time After Knee Extension Assessed by 31 Phosphorus Magnetic Resonance Spectroscopy (31P-MRS) Primary · Up to 2 hours after completion of drug infusion

Mitochondria function will be evaluated using 31P-MRS, which evaluates the concentration of phospho-creatine (PCr) and other phosphate-energy carrier molecules. After basal measurements, subjects will be asked to perform 90 seconds of knee extension followed by 4 minutes of rest. The exercise/rest cycle will be repeated 3 times. Magnetic resonance spectra will be used to calculate concentrations of inorganic phosphate (Pi), PCr, and adenosine triphosphate (ATP). The time constant tau of PCr recovery (time to achieve 66.3% maximal concentration during recovery) will be used to determine mitocho

Group	Value	95% CI
Icatibant	60.59	± 13.94
Placebo	62.66	± 29.4

Systolic Blood Pressure Secondary · 30 minutes before hemodialysis, during dialysis, and up to 1 hour after hemodialysis

Blood pressure will be monitored every 15 minutes, before, during, and after hemodialysis.

30 minutes before hemodialysis

Group	Value	95% CI
Icatibant	123.36	± 15.83
Placebo	125.27	± 25.04

during dialysis

Group	Value	95% CI
Icatibant	122.5454545	± 16.87224725
Placebo	122.18	± 23.23

up to 1 hour after hemodialysis

Group	Value	95% CI
Icatibant	119.09	± 19.06
Placebo	124.09	± 19.90

Adverse events — posted to ClinicalTrials.gov

Time frame: 6 months. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Icatibant

Serious: 0/11 (0%)

Deaths: 0/11

Placebo

Serious: 2/11 (18%)

Deaths: 0/11

Serious adverse events (2 terms)

Reaction	System	Icatibant	Placebo
Hospitalization for cardiac catheterization	Cardiac disorders	—	—
Hypovolemia	Gastrointestinal disorders	—	—

Other adverse events (2 terms — click to expand)

Reaction	System	Icatibant	Placebo
Patient was admitted for possible kidney transplant	Renal and urinary disorders	—	—
Arterious venous access thrombosis	Blood and lymphatic system disorders	—	—

Most-reported serious reactions: Hospitalization for cardiac catheterization, Hypovolemia.

Data from ClinicalTrials.gov NCT03177798 adverse events section.

Sponsor's own description

The overarching goal of this study is to determine the role of chronic kidney disease and the activation of the kallikrein-kinin system during hemodialysis on the development of mitochondrial dysfunction; the investigators will measure mitochondrial function using the gold standard method, 31-phosphorus magnetic resonance spectroscopy.

The investigators will test the hypothesis that endogenous bradykinin promotes mitochondrial dysfunction in patients undergoing hemodialysis. The investigators will first perform a randomized, placebo-controlled, double-blind, cross-over study measuring the effect of Icatibant (HOE-140), a bradykinin B2 receptor blocker, on mitochondrial function.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. The mitophagy pathway and its implications in human diseases.
   Wang S, Long H, Hou L, Feng B, et al · · 2023 · cited 484× · PMID 37582956 · DOI 10.1038/s41392-023-01503-7
2. A Systematic Review of Molecular Imaging Agents Targeting Bradykinin B1 and B2 Receptors.
   Lau J, Rousseau J, Kwon D, Bénard F, et al · · 2020 · cited 29× · PMID 32824565 · DOI 10.3390/ph13080199